Key points from the evidence

Summary

This evidence summary is based on 4 small observational studies. Treatment with fosfomycin trometamol was associated with a clinical success rate (defined as the resolution of symptoms after treatment) of between 77.8% and 94.2% in the 3 studies that reported this outcome. In 2 comparative studies, outcomes were similar in people whose urinary tract infections were treated with fosfomycin trometamol and other antibiotics.

No data on adverse events were available from the studies. More robust studies are needed to further evaluate the safety and efficacy of fosfomycin trometamol for treating urinary tract infections caused by multidrug-resistant bacteria.

Regulatory status: Fosfomycin trometamol (Monuril, Zambon) has a UK marketing authorisation for treating acute lower uncomplicated urinary tract infections. However, it is not distributed in the UK by the holder of the marketing authorisation; it needs to be imported if it is prescribed. Use of imported fosfomycin is unlicensed in the UK.

Clinical success rates were similar with fosfomycin trometamol and co-amoxiclav (n=65; 92.9% compared with 83.8%; significance not reported).

Clinical success occurred in 94.2% of people in 1 case series (n=52).

A second case series reported microbiological outcomes only (n=41).

Safety

Adverse events were not reported in 2 studies; the other 2 studies stated that no adverse events were reported.

The summary of product characteristics for fosfomycin trometamol states that it is 'generally well tolerated'.

The most common adverse effects reported are GI disturbances and skin rashes.

Patient factors

Fosfomycin trometamol is administered orally.

The number of doses of fosfomycin trometamol is generally between 1 and 3, which may help some people to adhere to treatment.

Resource implications

A single 3 g sachet of fosfomycin trometamol costs £62.10.

Key points

Fosfomycin trometamol (Monuril, Zambon) is a broad spectrum antibiotic that has a UK marketing authorisation for treating acute lower uncomplicated urinary tract infections. However, fosfomycin is not available commercially as a licensed product in the UK and, currently, the only means of obtaining it is to order from a 'specials' supplier. Brands include Monuril (Zambon; France, Italy and the Netherlands) and Monurol (Pharmazam; Spain and Zambon; USA). Use of these imported products is unlicensed in the UK.

The Management of infection guidance states that, following advice from a microbiologist, fosfomycin or nitrofurantoin should be considered for treating adults with uncomplicated urinary tract infections (no fever or flank pain) due to extended-spectrum beta-lactamase-producing Escherichia coli. If fosfomycin is used, a single 3 g dose is recommended in women. In men, a second 3 g dose should be taken after 3 days.

This evidence summary describes the efficacy and safety of fosfomycin trometamol for treating urinary tract infections caused by multidrug-resistant, including extended-spectrum beta-lactamase-producing, bacteria.

No randomised controlled trials were identified that assessed the clinical efficacy of oral fosfomycin for treating urinary tract infections caused by multidrug-resistant bacteria. Four small observational studies were identified that met the inclusion criteria for this evidence review.

The study by Senol et al. (2010) was a small prospective cohort study of 47 people with complicated lower urinary tract infections caused by extended-spectrum beta-lactamase-producing E. coli and treated with fosfomycin trometamol or a carbapenem. There was no statistically significant difference between fosfomycin trometamol and carbapenems in terms of clinical and microbiological success rates (77.8% compared with 95.0%, and 59.3% compared with 80.0% respectively).

Rodríguez-Baño et al. (2008) reported outcomes for 65 people with cystitis due to extended-spectrum beta-lactamase-producing E. coli which was treated with fosfomycin trometamol or co-amoxiclav. Clinical cure was seen in 92.9% of people taking fosfomycin trometamol and 83.8% of people taking co-amoxiclav; statistical significance was not reported.

The study by Neuner et al. (2012) was a retrospective chart review of 41 people who were in hospital and had a urinary tract infection due to a multidrug-resistant pathogen and who had received fosfomycin trometamol. Microbiological cure occurred in 24 people (58.5%). Clinical success was not reported.

The study by Pullukcu et al. (2007) was a retrospective case series of 52 people with lower urinary tract infections due to extended-spectrum beta-lactamase-producing E. coli treated with fosfomycin trometamol. Clinical and microbiological success occurred in 49 people (94.2%) and 41 people (78.8%) respectively.

Adverse events were not reported in 2 studies, and the other 2 studies stated that no adverse events were reported.

Randomised controlled trials of fosfomycin for treating urinary tract infections not specifically due to multidrug-resistant organisms have been carried out. A systematic review and meta-analysis of fosfomycin for cystitis, which included 27 randomised controlled trials, found that fosfomycin was as safe and as effective as other antibiotics (Falagas et al. 2010b). However, this study is not directly relevant to this evidence summary because it did not specifically assess fosfomycin treating urinary tract infections caused by multidrug-resistant bacteria.

The 4 studies that examined the efficacy and safety of fosfomycin trometamol for treating urinary tract infections caused by multidrug-resistant bacteria were limited by the fact that they were small observational studies. More robust studies are needed to further evaluate the safety and efficacy of fosfomycin for this indication.

Many people in the studies had complicated urinary tract infections and many were in hospital; therefore, care should be taken when applying the results to people with uncomplicated urinary tract infections in the community who are covered by the Management of infection guidance. Similarly, many people took repeated doses of fosfomycin trometamol, rather than a single dose.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.